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Effect of Ethanol on Intestinal Absorption of Theophylline

1974; Elsevier BV; Volume: 63; Issue: 6 Linguagem: Inglês

10.1002/jps.2600630604

1520-6017

Renu Koysooko, Gerhard Levy,

Antibiotics Pharmacokinetics and Efficacy

The purpose of this investigation was to deter mine directly the effect of ethanol on the absorption of theophylline from the small intestine of the rat. In the first part of the investigation, a 50-mg % solution of theophylline containing 0, 5, 10, or 20% ethanol was placed in a ligated segment of small intestine of anesthetized rats and sampled at intervals. Theophylline absorption was significantly increased by 5% ethanol and decreased by 20% ethanol. There was a positive rank-order correlation between theophylline absorption rate from the four solutions and water net flux. In the second part of the investigation, a segment of small intestine of anesthetized rats was perfused with theophylline solutions containing 0 or 2% ethanol. The concentration of ethanol was kept constant by continuous infusion of ethanol into the circulating perfusion solution. Theophylline absorption and water net flux were significantly increased by 2% ethanol. Intravenous infusion of ethanol at a rate sufficient to produce the same plasma concentration of ethanol as was observed upon intestinal perfusion with a solution containing 2% ethanol had no effect on theophylline absorption from the small intestine. The intestinal clearance of theophylline was independent of concentration in the 10-200-mg % range. Ethanol solutions without theophylline produced the same changes in water net flux as did the theophylline-ethanol solutions. It is concluded that the effect of ethanol on the intestinal absorption of theophylline is probably due to solvent drag, secondary to a change in water flux induced by alcohol.